Fluoxetine is a selective serotonin reuptake inhibitor approved for treatment of bulimia, obsessive-compulsive behavior, panic, premenstrual dysphoria, and major depressive disorder, with a variety of off-label uses. Both fluoxetine and its major metabolite, norfluoxetine, are pharmacologically active, and are reported together in this assay. Most individuals respond optimally when combined serum concentrations for both parent and metabolite are in the therapeutic range (120-300 ng/mL) at steady state. Due to the long half-lives of parent and metabolite (1-6 days), it may take several weeks for patients to reach steady-state concentrations. Fluoxetine is a potent inhibitor of the metabolic enzyme CYP2D6, with lesser inhibitory effects on CYP2C19 and CYP3A. Therapy with fluoxetine is therefore subject to numerous drug interactions, which is compounded by wide interindividual variability in fluoxetine pharmacokinetics. Measurement of the drug is useful for managing comedications, dose or formulation changes, and in assessing compliance. Side effects are milder for fluoxetine than for older antidepressants such as the tricyclics. The most common side effects of fluoxetine therapy include nausea, nervousness, anxiety, insomnia, and drowsiness. Anticholinergic and cardiovascular side effects are markedly reduced compared to tricyclic antidepressants. Fatalities from fluoxetine overdose are extremely rare.

Most individuals display optimal response to fluoxetine when combined serum levels of fluoxetine and norfluoxetine are between 120 and 300 ng/mL. Some individuals may respond well outside of this range, or may display toxicity within the therapeutic range, thus interpretation should include clinical evaluation. A toxic range has not been well established.